Natural whole blood is in short supply, and the shortage will probably increase. New methods for prolonged preservation of blood in the frozen state and improvements in storage in the liquid state have resulted in more efficient use of available blood in some areas, but the world-wide need for blood for transfusion still far exceeds the supply. Since it is unlikely that there will be any appreciable increase in supply, needs must be satisfied by substances other than natural blood or its derivatives. An artificial blood, available in unlimited quantities and free from infectious agents and antigens would be an extremely valuable therapeutic agent.
Emulsions of perfluoro compounds now seem likely to be successful as artificial blood. Perfluorochemical emulsion artificial bloods are free of infectious agents and antigens. (Hereinafter, perfluoro compound and perfluorochemical shall be used interchangeably). Blood typing of the recipient is unnecessary. However, such artificial bloods lack clotting factors, platelets, immunoglobulins and antibodies.
Perfluorochemical emulsions have been used sucessfully as substitutes for red blood cells in perfusing isolated animal organs and in the delivery of oxygen to the tissues of intact animals. Recently, an emulsion of perfluorochemicals was used in treating human subjects.
Although perfluoro compounds are chemically inert, they may adversely affect blood platelets and blood coagulation factors, resulting in thrombocytopenia (i.e., decrease in the absolute number of blood platelets) and disorders of blood coagulation. It has been found that the effects on platelets are likely due to unusual surface properties of perfluoro compounds, namely a very low surface tension. This effect can be overcome by coating the perfluoro compound particles with a substance which masks its surface activity.
Among the prior patents pertaining to artificial blood compositions the following are noted:
Miller et al, U.S. Pat. No. 4,133,874 is directed to water-soluble lipid-encapsulated hemoglobin.
Watanabe et al, U.S. Pat. No. 3,958,014; Yokoyama et al, U.S. Pat. No. 3,962,439; Moore et al, U.S. Pat. No. 4,105,798; and Yokoyama et al U.S. Pat. No. 4,252,827 pertain to emulsified oxygen-transporting particles of perfluoro compounds.
Prior artificial bloods have limited duration in the bloodstream. Within 2-4 days after transfusion of emulsified perfluoro compound particles, virtually all particles disappear from the circulation. Moreover, thrombocytopenia is often observed in laboratory animals after infusion. What is needed is a method for extending the effective life of the artificial blood composition in circulation.
An important problem concerning the clinical use of perfluoro compound emulsions is the retention of perfluoro compound in the tissues, mainly the liver and the spleen. The major route of perfluoro compound elimination is through the lungs. An increase in the time which the material remains in circulation results in increased elimination as expired gas, and hence a decrease in retention in the liver and spleen.